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1.
J Ultrasound ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581554

RESUMO

BACKGROUND: Rugby is a sport involving a great number of shoulder collisions. Traumatic stress of the shoulder can weaken the static stabilizers and promote major injuries as dislocation or full-thickness tears of the rotator cuff. The goal of this study is to evaluate the clinical and ultrasonographic dominant shoulder factures in a group of amateur rugby players, with no history of shoulder injuries, and to compare them with those of a control group. METHODS: 52 male subjects join in the study: 26 amateur rugby players and 26 subjects, which did not practice rugby or competitive sport. Clinical history was obtained from all subjects, followed by dominant shoulder physical and ultrasonographic exams. RESULTS: Rugby players showed a higher prevalence of positive clinical test, suggesting subacromial impingement than control group (p = 0.01). Among rugby group, five players (19,2%) showed positive test for radiculopathy (p = 0,02), and ten players (73,1%) reported shoulder pain needing pain-reliever drugs at list one time in the last six months (p = 0.001). In rugby group, ultrasound exams showed 23,1% degenerative changes and 30,8% tendon calcifications in supraspinatus tendons (p < 0.05). CONCLUSIONS: Uninjured dominant shoulder of rugby players shows higher prevalence of clinical and ultrasound changes compare to control. Some rugby players without history of cervical symptoms show positive clinical test of cervical radiculopathy. Clinical and ultrasonographic monitoring of the shoulder can play a role in prevention and knowledge of silent shoulder damage in these athletes.

2.
Diagnostics (Basel) ; 14(4)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38396420

RESUMO

Necrotizing pancreatitis is a complex clinical condition burdened with significant morbidity and mortality. In recent years, the huge progress of interventional endoscopic ultrasound (EUS) has allowed a shift in the management of pancreatic necrotic collections from surgical/percutaneous approaches to mini-invasive endoscopic internal drainage and debridement procedures. The development of lumen-apposing metal stents (LAMSs), devices specifically dedicated to transmural EUS interventions, further prompted the diffusion of such techniques. Several studies have reported excellent outcomes of endoscopic interventions, in terms of technical success, clinical efficacy and safety compared to surgical interventions, and thus endoscopic drainage of walled-off necrosis (WON) has become a fundamental tool for the management of such conditions. Despite these advancements, some critical unresolved issues remain. Endoscopic therapeutic approaches to WON are still heterogeneous among different centers and experts. A standardized protocol on indication, timing and technique of endoscopic necrosectomy is still lacking, and experts often adopt a strategy based on personal experience more than robust data from well-conducted studies. In this review, we will summarize the available evidence on endoscopic management of WON and will discuss some unanswered questions in this rapidly evolving field.

3.
RMD Open ; 10(1)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38296800

RESUMO

OBJECTIVE: Evaluate spondyloarthritis (SpA) incidence in inflammatory bowel diseases (IBD) between patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) and conventional DMARDs (cDMARDs) and define risk factors associated with SpA development. METHODS: Retrospective cohort study was conducted on patients with Crohn's disease (CD) or ulcerative colitis (UC) and divided into two cohorts: cDMARDs or bDMARDs/targeted synthetic (ts) DMARDs treated patients. Rheumatological assessment was performed in patients presenting musculoskeletal symptoms. Multivariate analysis and Kaplan-Meier curves were used to evaluate the adjusted SpA risk development. RESULTS: 507 patients were included in the study. 176 patients with CD received bDMARDs, 112 cDMARDs and 106 new SpA diagnosies were formulated. Females (OR 1.7 (95% CI 1.1 to 3), adjusted p=0.04), non-stricturing/non-penetrating phenotype (OR 2 (95% CI 1.1 to 3.4), adjusted p=0.01), psoriasis (OR 2.1 (95% CI 1 to 4.6), adjusted p=0.04) and non-infectious uveitis (OR 6.8 (95% CI 1.4 to 33.4), adjusted p=0.01) were associated with increased SpA risk development, while bDMARDs usage was protective (OR 0.4 (95% CI 0.2 to 0.8), adjusted p=0.01), statistically higher than cDMARDs throughout the entire follow-up (effect size 0.47). 98 patients with UC received b-tsDMARDs, 121 cDMARDs and 56 new SpA diagnoses were formulated. Females (OR 2.1 (95% CI 1 to 4.3), adjusted p=0.02) and psoriasis (OR 2.7 (95% CI 1 to 6.8), adjusted p=0.03) were associated with increased SpA risk development, while bDMARDs were protective for SpA development for up to 12 months of treatment compared with cDMARDs (p=0.03). CONCLUSIONS: bDMARDs treatment had an impact in reducing SpA development and clinical associated risk factors to transition from IBD to IBD-SpA emerged.


Assuntos
Antirreumáticos , Doenças Inflamatórias Intestinais , Psoríase , Espondilartrite , Feminino , Humanos , Estudos Retrospectivos , Antirreumáticos/efeitos adversos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Espondilartrite/complicações , Espondilartrite/tratamento farmacológico , Espondilartrite/epidemiologia , Psoríase/epidemiologia , Terapia Biológica/efeitos adversos
4.
Dig Liver Dis ; 56(1): 55-60, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37407314

RESUMO

Ulcerative colitis (UC)-related mucosal inflammation is characterized by the production of various autoantibodies with limited clinical relevance. Recent studies have shown that circulating levels of IgG against integrin αvß6 are increased in UC patients as compared to Crohn's disease (CD) patients and healthy controls (HC). The present study assessed the diagnostic value of circulating IgG anti-αvß6 in UC. Sera were prospectively collected from 108 outpatients with UC, 103 patients with CD, and 62 HC, and the levels of IgG anti-αvß6 were measured using a commercially available ELISA kit. The cut-off for positive results was defined as the 95th percentile of the values of the autoantibodies in HC serum samples. Levels of IgG anti-αvß6 were significantly higher in UC than in CD patients, including those with colonic localization, and HC. Fifty-six of the 108 (51.8%) UC patients had a positive test whereas only 17/103 (16.5%) patients with CD, and among these, 4/16 (25%) patients with colonic CD, were positive. In UC, there was no statistical difference between patients with IgG anti-αvß6 positivity and those negative in terms of clinical disease activity, fecal calprotectin values, and disease extent. The sensitivity, specificity, predictive positive value, and predictive negative value of the test to differentiate between UC and CD were 51.9% (C.I.42.4-61.3), 83.5% (C.I. 76.3-90.7), 76.7% (C.I. 67.0-86.4), and 62.3% (C.I. 54.2-70.4) respectively. Our study confirms that anti-αvß6 antibodies are demonstrable in the serum of the majority of UC patients and suggests the necessity of further research to understand if the anti-αvß6 antibody determination could have a place in the clinical decision-making of IBD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Humanos , Autoanticorpos , Imunoglobulina G , Biomarcadores
6.
Int J Mol Sci ; 24(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38068921

RESUMO

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents a promising anticancer agent, as it selectively induces apoptosis in transformed cells without altering the cellular machinery of healthy cells. Unfortunately, the presence of TRAIL resistance mechanisms in a variety of cancer types represents a major hurdle, thus limiting the use of TRAIL as a single agent. Accumulating studies have shown that TRAIL-mediated apoptosis can be facilitated in resistant tumors by combined treatment with antitumor agents, ranging from synthetic molecules to natural products. Among the latter, flavonoids, the most prevalent polyphenols in plants, have shown remarkable competence in improving TRAIL-driven apoptosis in resistant cell lines as well as tumor-bearing mice with minimal side effects. Here, we summarize the molecular mechanisms, such as the upregulation of death receptor (DR)4 and DR5 and downregulation of key anti-apoptotic proteins [e.g., cellular FLICE-inhibitory protein (c-FLIP), X-linked inhibitor of apoptosis protein (XIAP), survivin], underlying the TRAIL-sensitizing properties of different classes of flavonoids (e.g., flavones, flavonols, isoflavones, chalcones, prenylflavonoids). Finally, we discuss limitations, mainly related to bioavailability issues, and future perspectives regarding the clinical use of flavonoids as adjuvant agents in TRAIL-based therapies.


Assuntos
Antineoplásicos , Flavonoides , Neoplasias , Animais , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Ligantes , Neoplasias/tratamento farmacológico , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
7.
Cancers (Basel) ; 15(20)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37894350

RESUMO

A number of data indicate that the sources of different kinds of PDAC may be discovered at the transcription/transduction stage. RNA metabolism is manipulated at various steps by different RNA-binding proteins (RBPs), and the deregulation or irregular activity of RBPs is known to contribute to tumor promotion and progression. The insulin-like growth factor 2 mRNA-binding protein family (IMPs), and IMP1 in particular, has been linked with a poor prognosis in PDAC patients; however, little is known about its contribution in PDAC carcinogenesis. In this study, we investigated the function of IMP1 in PDAC. To evaluate IMP1 expression and correlation with PDAC prognosis, we utilized several public databases. Using a specific siRNA IMP1, we analyzed cell death and cell cycle progression in PDAC cell lines and 3D spheroids. The role of IMP1 was also evaluated in vivo in a Panc-1-derived tumor xenograft murine model. Public data suggest that PDAC patients with higher expression of IMP1 showed poor overall and progression-free survival. IMP1 silencing leads to reduced cell growth in PDAC cells and three-dimensional spheroids. Abrogation of IMP1 in PDAC cells showed lower levels of CDC25A, increased phosphorylation of the cyclin-dependent kinase (CDK)2, and accumulation of PDAC cells in the G1 phase. Immunoprecipitation experiments revealed that IMP1 binds CDC25A mRNA, thus controlling cell-cycle progression. Ultimately, we proved that suppression of IMP1 blocked in vivo growth of Panc-1 transferred into immunodeficient mice. Our results indicate that IMP1 drives the PDCA cell cycle and represents a novel strategy for overcoming PDCA cell proliferation.

8.
Expert Opin Emerg Drugs ; 28(3): 191-201, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37668153

RESUMO

INTRODUCTION: Despite the availability of a variety of therapeutic compounds and improved management strategies, one-third of UC patients with moderate-to-severe disease do not benefit from the existing treatments or experience drug-related side effects. This has boosted intensive research focusing on the development of new drugs for UC therapy. This article aims to summarize the available evidence on oral drugs, which are now being explored in clinical trials or are ready to enter the clinics. AREAS COVERED: From May 15 to June 11, we searched on PubMed using the keywords 'oral drugs ulcerative colitis,' 'ulcerative colitis clinical trials,' 'UC phase 2 and 3 trials' excluding case reports, case series, phase 1 and 4 studies, and studies about approved therapies. EXPERT OPINION: The findings discussed in this article suggest that the future treatment of UC patients will be probably characterized by the possibility of using various small-molecule drugs. All these new compounds, even those belonging to the same class, differ in terms of efficacy and safety. Identification of predictors of response could help optimize the efficacy and safety of these treatments, thus improving resource allocation through a pretreatment stratification of patients.


Assuntos
Colite Ulcerativa , Humanos , Colite Ulcerativa/tratamento farmacológico
9.
Eur J Immunol ; 53(11): e2350460, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37611637

RESUMO

Transforming growth factor (TGF)-ß1, a member of the TGF-ß superfamily, is produced by many immune and nonimmune cells and has pleiotropic effects on both innate and adaptive immunity, especially in the control of T-cell differentiation and function. Consistently, loss of TGF-ß1 function is associated with exacerbated T-cell-dependent inflammatory responses that culminate in pathological processes in allergic and immune-mediated diseases. In this review, we highlight the roles of TGF-ß1 in immunity, focusing mainly on its ability to promote differentiation of regulatory T cells, T helper (Th)-17, and Th9 cells, thus contributing to amplifying or restricting T-cell responses in health and human diseases (e.g., inflammatory bowel diseases, type 1 diabetes, asthma, and MS). In addition, we discuss the involvement of Smad7, an inhibitor of TGF-ß1 signaling, in immune-mediated disorders (e.g., psoriasis, rheumatoid arthritis, MS, and inflammatory bowel diseases), as well as the discordant results of clinical trials with mongersen, an oral pharmaceutical compound containing a Smad7 antisense oligonucleotide, in patients with Crohn's disease. Further work is needed to ascertain the reasons for such a discrepancy as well as to identify better candidates for treatment with Smad7 inhibitors.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Oligonucleotídeos Antissenso/farmacologia , Oligonucleotídeos Antissenso/uso terapêutico , Proteína Smad7/genética , Proteína Smad7/metabolismo , Proteína Smad7/uso terapêutico , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
10.
Autoimmun Rev ; 22(10): 103410, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37597601

RESUMO

The term "immune-mediated inflammatory diseases (IMIDs)" refers to several inflammatory pathologies of multifactorial etiology and involving either simultaneously or sequentially more organs. IMIDs share some common pathogenic mechanisms, which account for some similarities in the clinical course and the impact that these diseases may have on other organs and systems of the body. However, there are some differences in the IMID-associated pathological process, including the synthesis and function of multiple inflammatory cytokines, which are supposed to perpetuate the tissue-damaging inflammation. This justifies the different indications and responsiveness to corticosteroids, immunosuppressors, small molecules, and biologics. Many individuals with IMIDs are, however, intolerant, or unresponsive to the current drugs, thus suggesting the necessity of novel therapeutic approaches, such as the combination of compounds that either inhibit more immuno-inflammatory networks selectively or simultaneously suppress inflammatory signals and activate counter-regulatory pathways. In this article, we highlight the most relevant features of IMIDs and discuss how clinicians can combat the detrimental immune response in such disorders.


Assuntos
Doenças Autoimunes , Humanos , Agentes de Imunomodulação , Inflamação
11.
BMC Anesthesiol ; 23(1): 260, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37542218

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an interventional procedure that requires deep sedation or general anaesthesia. The purpose of this prospective observational study was to assess the feasibility and safety of deep sedation in ERCP to maintain spontaneous breathing. METHODS: This is a single-centre observational prospective cohort study conducted in a tertiary referral university hospital. All consecutive patients who needed sedation or general anaesthesia for ERCP were included from January 2021 to June 2021. Deep sedation was achieved and maintained by continuous infusion of an association of propofol and remifentanil. The primary endpoint was to assess the prevalence of major anaesthesia-related complications, such as arrhythmias, hypotension, gas exchange dysfunction, and vomiting (safety endpoint). Secondary endpoints were: (a) to assess the prevalence of signs of an insufficient level of sedation, such as movement, cough, and hiccups (feasibility endpoint): (b) time needed to achieve the target level of sedation and for recovery from anaesthesia. In order to do so we collect the following parameters: peripheral oxygen saturation, fraction of inspired oxygen, noninvasive systemic blood pressure, heart rate, number of breaths per minute, neurological functions with the use of the bispectral index to determine depth of anaesthesia, and partially exhaustive CO2 end pressure to continuously assess the ventilatory status. The collected data were analysed by several tests: Shapiro-Wilk, Student's t, Tuckey post-hoc, Wilcoxon rank-sum and Kruskall-Wallis ran. Statistical analysis was performed using Stata/BE 17.0 (StataCorp LLC). RESULTS: 114 patients were enroled. Eight patients were excluded because they did not meet the inclusion criteria. We found that all patients were hemodynamically stable: intraoperative mean systolic blood pressure was 139,23 mmHg, mean arterial pressure was on average 106,66 mmHg, mean heart rate was 74,471 bpm. The mean time to achieve the target level of sedation was 63 s, while the mean time for the awakening after having stopped drug infusion was 92 s. CONCLUSIONS: During ERCP, deep sedation and analgesia using the association of propofol and remifentanil and maintaining spontaneous breathing are safe and feasible, allowing for a safe and quick recovery from anaesthesia.


Assuntos
Sedação Profunda , Propofol , Humanos , Propofol/efeitos adversos , Remifentanil , Hipnóticos e Sedativos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estudos Prospectivos , Sedação Profunda/métodos , Estudos de Viabilidade
12.
Cancers (Basel) ; 15(15)2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37568619

RESUMO

A higher frequency of mucinous and signet-ring cell colonic adenocarcinoma has been reported in inflammatory bowel disease (IBD). The primary aim was to investigate the frequency of mucinous and signet-ring cell colorectal adenocarcinoma in patients with IBD (Cases) versus age-matched non-IBD Controls. The secondary aims were to compare the characteristics of these two histotypes of colorectal cancer (CRC) in IBD patients vs. Controls and to search for specific risk factors in IBD. In a case-control study, all IBD patients with CRC diagnosed from 2000 to 2022 were enrolled and matched for age (1:2) with non-IBD Controls with CRC. The study population included 120 CRC patients (40 IBD, 80 Controls). In IBD, CRC included standard adenocarcinoma in 23 (57.5%) patients mucinous/signet-ring cell adenocarcinoma in 17 (42.5%) patients. The proportion of mucinous/signet-ring cell adenocarcinoma was higher in IBD than in Controls (17 [42.5%] vs. 18 [22.5%]; p = 0.03). In rectal CRC, the proportion of mucinous/signet-ring cell adenocarcinoma was higher than standard adenocarcinoma in IBD (8 [47.1%] vs. 4 [17.4%]; p = 0.04) but not in Controls (4 [22.2%] vs. 20 [32.2%]; p = 0.59). In rectal CRC, the proportion of these two histotypes was higher in Cases than in Controls (8/12 [66.6%] vs. 4/24 [16.6%]; p = 0.008), with no risk factors identified in IBD. CRC was more frequently represented by mucinous/signet-ring cell adenocarcinoma in IBD than in age-matched non-IBD Controls. In IBD, these two CRC histotypes were more frequent in the rectum.

14.
Cancers (Basel) ; 15(13)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37444471

RESUMO

Current endoscopic surveillance programs do not consider inflammatory bowel disease (IBD)-associated post-inflammatory polyps (pseudopolyps) per se clinically relevant, even though their presence seems to increase the risk of colorectal cancer (CRC). However, it remains unclear whether the link between pseudopolyps and CRC is indirect or whether some subsets of pseudopolyp-like lesions might eventually undergo neoplastic transformation. This study aimed to assess the frequency and predictors of dysplasia in pseudopolyp-like lesions in a population with long-standing colonic IBD. This was a retrospective, single-center study including patients with a colonic IBD (median disease duration of 192 months) and at least a pseudopolyp-like lesion biopsied or resected in the period from April 2021 to November 2022. One hundred and five pseudopolyps were identified in 105 patients (80 with ulcerative colitis and 25 with Crohn's disease). Twenty-three out of 105 pseudopolyp samples (22%) had dysplastic foci, and half of the dysplastic lesions were hyperplastic. Multivariate analysis showed that the age of the patients (odds ratio (OR) 1.1; p = 0.0012), size (OR 1.39; p = 0.0005), and right colonic location (OR 5.32; p = 0.04) were independent predictors of dysplasia, while previous exposure to immunosuppressors/biologics and left colonic location of the lesions were inversely correlated to dysplasia (OR 0.11; p = 0.005, and OR 0.09; p = 0.0008, respectively). No differences were seen between ulcerative colitis and Crohn's disease patients. Lesions with a size greater than 5 mm had a sensitivity of 87% and a specificity of 63% to be dysplastic. These data show that one-fourth of pseudopolyp-like lesions evident during surveillance colonoscopy in patients with longstanding IBD bear dysplastic foci and suggest treating such lesions properly.

15.
Eur J Gastroenterol Hepatol ; 35(9): 948-954, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37505974

RESUMO

BACKGROUND: The long-term outcome of inflammatory bowel disease (IBD) patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is under investigation. AIM: To assess, in a prospective study, whether a recent SARS-CoV-2 infection increases the risk of IBD relapse within 12 months. METHODS: From March to April 2021, all IBD patients with recent (<2 months) SARS-CoV-2 infection (Cases) were enrolled. For each enrolled Case, four IBD Controls with no history of infection were considered. Clinical course of IBD was recorded for 12 months. Inclusion criteria: well defined diagnosis of IBD; age ≥18 and ≤85 years; 12-month follow-up; consent. Exclusion criteria: incomplete data; SARS-CoV-2 infection after enrollment. Additional inclusion criteria: recent SARS-CoV-2 infection for Cases; no history of SARS-CoV-2 infection for Controls. Data expressed as median [range]. Statistical analysis: Student-t-Test, Mann-Whitney U-test, χ2 test, multivariate logistic regression model [odds ratio (95% confidence interval)], Kaplan-Meier curves. RESULTS: One hundred forty-three IBD patients were enrolled. The analysis included 118 patients (22 met the exclusion criteria, three lost at follow-up): 29 (24.6%) Cases and 89 (75.4%) Controls. Demographic and clinical characteristics were comparable between groups. During the 12-month study, the frequency of IBD relapse was comparable between Cases and Controls [8 (27%) vs 19 (21%); P = 0.65]. At univariate analysis, SARS-CoV-2 infection was not a risk factor for IBD relapse within 12 months [1.5 (0.6-3.9); P = 0.34]. At multivariate analysis, IBD activity at baseline was the only risk factor for relapse [3.2 (1.1-9.1); P = 0.03]. Kaplan-Meier curves showed that survival from IBD relapse was comparable between Cases and Controls (P = 0.33). CONCLUSION: In a prospective 12-month study, a recent SARS-CoV-2 infection did not increase the risk of clinical relapse of IBD in the long term.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Humanos , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Prospectivos , Fatores de Risco , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia
16.
Biomedicines ; 11(7)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37509654

RESUMO

The intestinal epithelial barrier plays a key role in the absorption of nutrients and water, in the regulation of the interactions between luminal contents and the underlying immune cells, and in the defense against enteric pathogens. Additionally, the intestinal mucus layer provides further protection due to mucin secretion and maturation by goblet cells, thus representing a crucial player in maintaining intestinal homeostasis. However, environmental factors, such as dietary products, can disrupt this equilibrium, leading to the development of inflammatory intestinal disorders. In particular, ultra-processed food, which is broadly present in the Western diet and includes dietary components containing food additives and/or undergoing multiple industrial processes (such as dry heating cooking), was shown to negatively impact intestinal health. In this review, we summarize and discuss current knowledge on the impact of a Western diet and, in particular, ultra-processed food on the mucus barrier and goblet cell function, as well as potential therapeutic approaches to maintain and restore the mucus layer under pathological conditions.

17.
Genes (Basel) ; 14(7)2023 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-37510322

RESUMO

Several studies have investigated the role of genetics in anterior cruciate ligament (ACL) rupture, often returning conflicting results. The present pilot study aimed to analyze the association between six Single Nucleotide Polymorphisms (SNPs) (rs1800012; rs12722; rs13946; rs240736; rs970547; and rs4870723, located on the COL1A1, COL5A1, COL12A1, and COL14A1 genes), and ACL rupture, among Italian athletes. A hypothesis-driven association study was conducted. In total, 181 male and female athletes (n = 86 injured; n = 96 non-injured) were genotyped for the prioritized variants. All polymorphisms were genotyped using PCR RFLP, with the only exception being the rs1800012 on the COL1A1 gene, which was detected using MTPA PCR. The allele frequency distribution fell within the worldwide range. Despite the evident population variability, no selective pressure signals were recorded using PBS analysis. No significant difference was detected between the cases and controls for any of the SNPs (rs1800012; rs13946; rs240736; rs970547, and rs4870723) included in the analyses (p > 0.008, Bonferroni-adjusted for multiple comparisons). Moreover, no significant differences were found when males and females were assessed separately. Further investigations based on a larger sample size are needed, in order to draw solid conclusions for the influence between collagen genes and ACL rupture.


Assuntos
Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Humanos , Masculino , Feminino , Projetos Piloto , Lesões do Ligamento Cruzado Anterior/genética , Colágeno/genética , Atletas
18.
Inflamm Bowel Dis ; 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37478412

RESUMO

BACKGROUND: Oral and rectal formulations of 5-aminosalicylic acid are the first-line therapy for mild-to-moderate, distal ulcerative colitis (UC), but such a treatment is not effective in one-third of patients. Niclosamide is a small molecule, developed and approved as an orally administered drug to treat helminthic infections, with an excellent safety profile. Preclinical work showed that niclosamide is an anti-inflammatory agent, thereby providing the rationale to explore its safety and efficacy in patients with UC. This phase 1, open-label trial was aimed at assessing the safety of niclosamide formulated as an enema in patients with mild-to-moderate, distal UC, who relapsed on maintenance therapy with oral and/or rectal 5-aminosalicylic acid. METHODS: Seventeen patients with active UC received niclosamide enema (150 mg/60 mL) twice a day for 6 weeks. The primary endpoint was the safety of niclosamide treatment. Secondary endpoints included clinical remission and improvements in endoscopic Mayo/histologic scores. Endoscopic remission percentages exclude participants meeting criteria at baseline for endoscopic remission. RESULTS: Niclosamide was well tolerated by all 17 patients that were enrolled and treated. No serious adverse event was registered. Fifteen mild adverse events were registered in 6 patients and considered to be unrelated to the treatment. Clinical remission was achieved in 10 (59%) of 17 patients. Improvements of endoscopic Mayo score and histologic Geboes score were seen in 7 (58%) of 12 and 7 (41.2%) of 17 patients, respectively. CONCLUSIONS: Niclosamide enema treatment is safe and well tolerated. Niclosamide improves clinical symptoms and endoscopic/histologic signs of UC; however, appropriately designed placebo-controlled clinical trials are required to confirm efficacy.

20.
Dig Liver Dis ; 55(12): 1652-1657, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37258331

RESUMO

BACKGROUND: Intestinal ultrasonography (US) allows for the characterization of the intestinal lesions and provides information on transmural inflammation. The aim of the study was to assess the clinical relevance of echopattern and correlation with Crohn's disease (CD) behavior and activity. METHODS: We performed a prospective study including CD patients assessed by intestinal US. The echopattern was classified as hypoechoic, hyperechoic and stratified. Color-doppler US was also performed in the thickest segment. RESULTS: One hundred CD patients were enrolled. The hypoechoic echopattern was significantly correlated with penetrating behavior (r = 0.44, p<0.0001), active disease (r = 0.21, p = 0.034), C-reactive protein/Fecal Calprotectin (r = 0.31, p = 0.004; r = 0.34, p = 0.031, respectively) and steroids (r = 0.33, p = 0.0008). Hypoechoic echopattern was associated with younger age than stratified (p = 0.046) and hyperechoic (p = 0.018) echopatterns. Bowel wall thickness was greater in the hypoechoic group than in the hyperechoic/stratified groups (p = 0.011 and p<0.0001, respectively). Hypoechoic echopattern was associated with fistulas (r = 0.52, p<0.0001) and increased vascularization (r = 0.32, p = 0.001). The hyperechoic echopattern showed a significant correlation with stricturing disease and an inverse correlation with fistulas. During a follow up period of 6 months, patients with hypoechoic echopattern had an increased risk of biological therapy need or surgery. CONCLUSIONS: The characterization of bowel wall echopattern allows for the identification of different CD behaviors.


Assuntos
Doença de Crohn , Fístula , Humanos , Doença de Crohn/complicações , Estudos Prospectivos , Intestinos/patologia , Inflamação/complicações , Fístula/complicações , Fístula/patologia
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